Facial Growth PDF

FACIAL GROWTH - To describe the process of facial growth and development ​ - Starts week 4 w 5 swellings around stomodeum (primitive mouth) - Max and mandib swellings from 1^st^ pharyngeal arch -\> lat each side of stomodeum - Mandib swellings form lower border + 5^th^ - Frontonas...

FACIAL GROWTH - To describe the process of facial growth and development ​ - Starts week 4 w 5 swellings around stomodeum (primitive mouth) - Max and mandib swellings from 1^st^ pharyngeal arch -\> lat each side of stomodeum - Mandib swellings form lower border + 5^th^ - Frontonasal process forms upper border of stomodeum - Max swellings form upper border of stomodeum - Max swellings grow forwards + move closer together to fuse at midline - Nasal placode -\> 2 thickenings on frontonasal process - Failure of max swelling fusion = unilateral/bilateral cleft lip - Max + mandib swelling fusion = cheeks -\> reducing mouth width Formation of palate: - Intermaxillary process -\> prim palate + pre-maxilla + front of ant palate (4 max incisors) + nasal septum - Week 7 = thin extensions form in inner wall of max process -\> palatine shelves -\> form initially on either side of lat tongue - Palatine shelves rotate upwards to midline as tongue lowers - Week 8 + 9 = shelves fuse to each other + prim palate + lower border of nasal septum Bone formation + growth: - Intramembranous ossification = form bone in membrane - Endochondral ossification = bone replace cartilage - Bone can form w both methods - Intramembranous = embryo development in sheets - Calvarium, facial bones, most of mandible, clavicle -\> intramembranous - Bones of face + skull joined by sutures - Bony infill @ sutures = response to force separating bones on either side - Growth causes mass of bone to move relative to neighbours = displacement - Remodelling + displacement can occur simultaneously on same bone - Cartilage in mandib condyle diff to rest of body - Condylar cartilage grows in response to other facial structures Control of craniofacial growth: - Genetic control greater for anteroposterior growth compared to vertical growth Theories: Sutural theory (Sicher): - Sutures have innate growth potential - Suture pushed bones apart - Not true -\> transplanted suture did nothing - Stretched suture = growth - They respond w passive deposition Cartilaginous theory (Scott): - Prim determinant for growth = cartilage - Transplant nasal septum cartilage into other tissues = some growth - 75% no impairment in growth in condylar fracture in growing children Functional matrix theory (Moss) -- capsular + periosteal matrices: - Genetic control expressed in soft tissues -\> determines size and shape of bone - 2 types of matrices -\> periosteal + capsular - Periosteal -\> teeth, muscles, blood vessels, nerves - Microskeletal unit has own periosteal matrix - Capsular matrix -\> organs - Congenital absence of eye = diminutive and rudimentary orbit Likely that both capsular + functional matrix theories play part in craniofacial growth Postnatal craniofacial growth - As face enlarges -\> grows forwards + downwards - Calvarium, cranial base, maxilla + mandible grow differently -\> finish by 7yo - face grows slows in puberty - max growth pattern closer to neural growth -\> declines at 12yo - max complex growth important for position of upper teeth - max grows downward and forward until 7yo by drift + remodelling - downward growth -\> drift of hard palate + vertical development of alveolar process as teeth erupt and root forms - lat growth = displacement of halves of max + infill at mid palatal suture - max complex slows at 7yo and basically stops at 12yo - mandib follows somatic growth -\> periosteal activity - alveolar process adds to vert height - mandible displaced forwards by tongue growth - remodelling = ↑ width posterior mandible + length + prominent chin - growth occurs 2-3mm mandib body -\> doubles at puberty - slows down 17yo girls 19yo boys - facial growth never completely stops Growth prediction: - bone maturation on hand-wrist radiographs poor correlation to jaw growth -\> better assessment using cervical vertebrae - To reveal different skeletal types and the corresponding general facial patterns ​ Assessed in 3 planes: anteroposterior, vertical, transverse - To define the epigenetics and its impact on facial growth and development ​ - Study of how cells control gene activity w/o changing gene sequence - Stable, heritable traits not explained by changes in DNA - Leads to individual differences in appearance, physiology, cognition + behaviur -\> phenotype - Genes responsible for craniofacial structures are basically the same but every face is unique - Mechs: histone modification - Neural crest cells origin of facial structures - Environment signals reach neural crest cell to activate chromatin state - To reveal the facial differences between male and female   ​ CHICKS DUDES -------------------------------------- ------------------------------------- More prominent eyes + cheeks \~2.4mm More prominent nose + mouth \~2.7mm More v shaped mandible Smaller nasiolabial angle Fuller lips Stronger forehead Lips closer to nose Flatter cheekbones GROWTH OF FACE - Changes in shape of the head with growth - Face grows larger w head - Most in height then depth then width - On avg mandib grows more in A-P than max (antero-posterior) A diagram of a line Description automatically generated with medium confidence - On avg ANB gets smaller by 1° btw 11-20 - \~5% of population changes ANB by 6° - Jaw rotates as the grow -\> masked by remodelling - Downward/forward growth  - Most ppl have jaw relationship that stays the same w growth - Types of bone growth in the jaws - Endochondral: replacement of cartilage -\> cranial base of synchondroses, mandib condyle - Intramembranous: periosteal remodelling at surface and at sutures - Surface remodelling -\> mandib - cartilaginous -\> mandib condyle - synchondrosis -\> cranial base mandib growth: - dev in membrane, ossification intramembranous - secondary cartilage forms -\> condylar cartilage - later growth + extensive remodelling due to periosteal activity bone growth from external influence: - periosteal/sutral growth can be influenced by pressure and tension - periodontal remodelling from orthodontic forces - Control & rate of growth - Mainly genetic - Partly environmental - Nurtrition -\> softer foods = smaller jaws - Mouth breathing -- small effect - Bottle feeding -- maybe no effect - Jaw/tongue/lip exercises/cranial massage -- no evidence Tanner growth curves: - Used to monitor stature -\> indicates facial growth Growth velocity: - Steady decrease in velocity from birth - Brief reversal in velocity in puberty - Declines rapidly after pubertal growth spurt - Ability to predict & influence growth Can we predict growth? - Chronological age - Dental age - Secondary-sexual characteristics - Standing height - Growth velocity - Cervical vertebral maturation - Hand-wrist radiograph Can ortho treatment influence growth? - Kinda - Short term yes - Long term no - E.g. restrain max growth fr extreme class II case - Nothing can restrain forward growth of mandib - The clinical significance of growth - Unpredictable variation of skeletal change large effect on treatment - Success/failure can be due to unusual growth - Excessive vert growth = open bite formation - Treat class III later - Treat II earlier - Growth needed for spontaneous alignment - Ortho surgery + implants should be after growth stops - Not much rotation after growth - Develops btw week 6-12 - Fusion of palatal shelves - Dev from 1^st^ pharyngeal arch + frontonasal process - Formed from 3 processes: 2 maxillary processes 2 palatine processes of max processes Primitive palate formed from intermaxillary process (premaxilla) - Palate mesoderm -\> intramembranous ossification -\> hard palate formation - No ossification in posterior part = soft palate - Muscles of soft palate derived from 4^th^ pharyngeal arch - Defective fusion of processes = cleft palate - Bilateral = failure of fusion of both palatine processes + premaxilla = Y shaped cleft - Unilateral = non-fusion of one side of palatine process of maxilla w premaxilla - Incomplete = cleft limited to soft/hard palate or bifid uvula - Cleft lip = cleft of primary palate anterior to incisive foramen -\> lack of fusion of medial nasal processes of frontal nasal prominence w maxillary process - Nose cleft = intermaxillary segments fail and/or lateral nasal process fail to fuse Cleft as part of syndrome: - Ven der Woudes: lip pit, missing teeth, cleft palate, delayed language dev - Pierre Robin anomlad: micrognathia, natal teeth, glossoptosis, high arched/cleft palate - Di George Syndrome (velocardiofacial): wide eyes, distinctive ears, congenital heart defect, infection prone Cleft epidemiology: - 1:700 UK - 70% non-syndromic - Male : female = 2:1 - L: R = 2/3:1/3 Microform cleft: - Looks like little dent - Muscle tissue underneath can be affected -\> surgery Submucous cleft palate: - No midline/no muscle - Associated w bifid/cleft uvula - Post nasal spine almost always missing - Common speech problems Prob in dent: - Feeding - Hearing - Speech - Disruption of face growth - Disruption of dent dev + dent anomalies - Psychosocial Local dent problems: - Congenital missing teeth - Hypodontia - Oligodontia - Hyperdontia - Presence of natal/neonatal teeth - Anomalies of tooth morph -\> microdontia, macrodontia - Enamel hypoplasia - Poor periodontal support -\> early teeth loss - Gemination - Dilacerations Ortho problems: - Class III - Ant/post crossbite - Spacing + crowding Pre-natal diagnosis: - 81% of cleft lip diagnosed before birth - Cleft palate almost impossible to identify before birth Management: Birth: - Counselling - Feeding plate - Pre-surgery assessment 3m: - Primary lip repair 9-18m: - Palate repair 1-3y: - Speech therapy 3-6y: - Speech therapy - Masednoscopy and/or pharyngoplasty 8-9y: - Initial interventional ortho - Prep for alveolar bone grafting 10y: - Alveolar bone grafting 12-14y: - Definite ortho 17-20y: - Orthognathic surgery - Nasal revision surgery Impressions: - Taken to form part of the cleft record - Compares cleft in future - Part of CSAG audit Pre-surgical orthopaedics: - Maxillary strapping - Taping - Nasoalveolar moulding appliances Aims of surgery: - Restore normal anatomy - Minimise adverse effects - Reconstruct normal muscle - Make cleft unrecognisable Surgery: "rule of 10" - Primary repair around 10w - Weigh 10lb - Haemoglobin 10g - White count no higher than 10k - At least 10 weeks of age Alveolar bone grafting: - Timed to precede canine eruption on cleft side - Around 11y - Makes bony bridge across cleft so canine can erupt into new bone and to support periodontium Orthognathic surgery: - 18y+ - Almost always to correct class III - Can compromise velopharyngeal function CLINICAL CLEFT - To explain what cleft of the lip and palate is - Anatomical anomaly from failure of fusion of dentofacial development - 65% of anomolys affecting head and neck - 1:700 - High prevalence in Asians - Increasing prevalence - Family history influence - To describe the epidemiology, factors and diagnosis for cleft lip and palate - 1/20 chance for unaffected parents having child w this anomaly - If either parent have it 2-8% - Males\>females - LHS\>RHS - Might have environmental factors - Drugs can increase chance; vit A, heroin, anticonvulsant drugs, folic acid deficiency, steroid therapy - To relate the causes to the stage of foetal development - Polygenic inheritance w threshold - Secondary palate makes 2 shelves that are vertical to either side of tongue - Tongue lowers and shelves elevate to join at midline - Happens at 9-10w of pregnancy - Tongue fail to drop/fusion fail/breakdown of joint = cleft - Can very in size Cleft subdivided based on anatomical limit: - Primary palate = lip + alveolus - Lip + palate cleft - Palate only  Lip + cleft palate: - Complete cleft = communicates directly w nasal cavity - Unilateral cleft = minor segment of alveolus moves palatally -\> collapses inwards -\> makes cleft larger Cleft palate only: - Only secondary palate involved - May have submucous cleft where muscle isn't joined but mucosa is intact - To describe the stages of early treatment in children Case management: - Ante-natal (during preg) care = defects detected - If cleft is diagnosed -\> referral to cleft team for counselling - Can also be diagnosed on birth -\> asap referral to cleft team Cleft issues: - Each cleft = different problems -\> functional + aesthetic - Immediate priority = breathing + feeding - Breathing problems = retrognathic mandib - Common w Piere-Robin syndrome - Special feeding bottles (rosti) and feeding positions - Early lip surgery = good aesthetics. Speech development, feeding, intact dentition CLP team: - Orthodontist - Maxillofacial surgeon - Plastic surgeon - Speech therapist - Ear, nose, throat surgeon - Specialist health visitor Palate repair takes around 6 months Lip repair usually btw 6-12 weeks May have some hearing impairment -\> compromised muscles surrounding inner auditory meatus Othro implications: - Hypodontia - Supernumerary - Microdontia - Abnormal tooth size/shape - Impacte max canines - Ectopic eruption og 6's - Enamel hypoplasia - Crossbite - Bone defect - Class III incisor PATHOGENESIS OF COMMON CHILDHOOD VIRAL DISEASES - Report on the basic viral taxonomy 2021 onwards virus needs binomial nomenclature Virus: - Broad term - Infectious at all stages - Taxonomic classification Virion: - Complex and complete manifestation - Viral genome + capsid + envelope - Transmitted form Pleomorphism: - Helical - Spherical - Polyhedral - Complex Viral characteristics: - Obligatory intracellular parasites Viral structure: - Viral attachment proteins - Envelope - Matrix protein - Overview key principles in the pathogenesis of viral disease Lytic cycle:  **Attachment**: The virus attaches to the surface of a specific host cell using proteins that bind to receptors on the cell\'s surface.  **Entry**: The virus injects its genetic material (DNA or RNA) into the host cell.  **Replication**: The viral genetic material takes over the host cell\'s machinery, directing it to make viral components like proteins and new copies of the viral genome.  **Assembly**: New viral particles are assembled from the replicated genetic material and proteins within the host cell.  **Lysis and Release**: The host cell bursts (lyses), releasing new virus particles that can go on to infect other cells. Lysogenic cycle:  **Attachment and Entry**: The virus attaches to a host cell and injects its genetic material (DNA or RNA) into the cell.  **Integration**: The viral DNA integrates into the host cell\'s DNA, becoming a **prophage** (in bacteriophages) or **provirus** (in other organisms).  **Dormancy**: The viral DNA remains inactive and is copied along with the host DNA as the cell divides. This way, the virus\'s genetic material is passed on to daughter cells without causing damage.  **Activation**: Under certain conditions (like stress or UV light), the viral DNA may be triggered to exit the host DNA and enter the **lytic cycle**. The virus then begins replicating and assembling, eventually causing cell lysis. Acute infection: - Recovery - Progression to chronic - Death Chronic: - Silent infection for life - Long silent period before disease - Reactivation - Relapses + exacerbation - Neoplastic changes - Describe how cells may respond to viral infection **Detection of Viral Infection** - **Pattern Recognition Receptors (PRRs)**: Cells use specialized receptors, like **Toll-like receptors (TLRs)** and **RIG-I-like receptors**, to detect viral molecules, such as viral RNA or DNA. PRRs are located on the cell surface or within cellular compartments, allowing them to detect viral presence promptly. **2. Antiviral Interferon Response** - **Interferon Production**: Upon detecting viral material, infected cells release **type I interferons** (IFN-α and IFN-β). Interferons act as signaling molecules that alert neighboring cells to the infection and initiate antiviral defenses. - **Antiviral State in Neighboring Cells**: Interferons bind to receptors on nearby cells, activating genes that inhibit viral replication. This creates an "antiviral state" in surrounding cells, making it harder for the virus to spread. **3. Inhibition of Viral Replication** - **Antiviral Proteins**: Interferon signaling activates the production of **antiviral proteins** in both infected and neighboring cells. These proteins, such as **protein kinase R (PKR)** and **RNase L**, interfere with viral replication by degrading viral RNA, inhibiting protein synthesis, or modifying cellular processes that viruses rely on. **4. Activation of Apoptosis (Programmed Cell Death)** - **Apoptotic Response**: Many infected cells activate programmed cell death (apoptosis) in response to viral infection. By undergoing apoptosis, the cell sacrifices itself to prevent the virus from replicating further. This is regulated by proteins like **p53** and caspases, which initiate and execute the cell death program. - **Cytotoxic T Cell-Induced Apoptosis**: **Cytotoxic T cells** (a part of the adaptive immune response) recognize viral peptides presented on the surface of infected cells and induce apoptosis through the release of cytotoxic molecules (e.g., perforin and granzyme). **5. Autophagy** - **Autophagy Pathway**: Cells can use **autophagy**, a process that involves engulfing and degrading parts of the cytoplasm, including viral particles. This helps contain the virus within cellular compartments, where it can be degraded and presented to the immune system. **6. Antigen Presentation to Activate Immune Cells** - **MHC Presentation**: Infected cells display viral peptides on their surface using **major histocompatibility complex (MHC) molecules**. This presentation is crucial for activating immune cells, such as **helper T cells** (which coordinate the immune response) and **cytotoxic T cells** (which target infected cells). - **NK Cell Activation**: Some viruses interfere with MHC presentation to avoid detection, but **natural killer (NK) cells** can recognize cells with low MHC expression and target them for destruction. **7. Production of Inflammatory Cytokines** - **Cytokine Release**: Infected cells and immune cells release **cytokines** like interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interferons to amplify the immune response. This attracts more immune cells to the site of infection, enhancing the body's ability to contain and eliminate the virus. - Describe general features of the course of viral infections **1. Entry and Incubation Period** - **Viral Entry**: Viruses enter the body through mucosal surfaces (like the respiratory tract, digestive tract, or urogenital tract), breaks in the skin, or via direct inoculation (such as insect bites or injections). - **Incubation Period**: This is the time between viral entry and the appearance of symptoms. During this period, the virus begins replicating within the host cells, usually without causing noticeable symptoms. The length of incubation varies depending on the virus and the host\'s immune response. **2. Prodromal Phase** - **Early Symptoms**: The prodromal phase is marked by the appearance of early, nonspecific symptoms (e.g., fever, malaise, body aches). These symptoms are often a result of the host's immune response, particularly the release of inflammatory cytokines like interferons. **3. Acute Phase** - **Peak Viral Replication**: During the acute phase, the virus replicates at a high rate, and specific symptoms related to the virus appear. This phase is characterized by tissue damage, immune response, and symptoms like cough, rash, or diarrhea, depending on the target cells and organs. - **Host Immune Response**: The innate immune system is active, releasing interferons and activating natural killer (NK) cells, while the adaptive immune response begins to ramp up, with T cells and antibodies targeting the virus. - **Symptom Severity**: Symptoms may range from mild to severe, and in some cases, life-threatening complications may arise if vital organs are affected (e.g., viral pneumonia, encephalitis). **4. Resolution or Persistence** - **Resolution**: In many cases, the immune system successfully eliminates the virus. **Cytotoxic T cells** kill infected cells, while **antibodies** neutralize free virus particles. Symptoms gradually resolve, and the host returns to health. - **Persistence**: Some viruses evade the immune system, leading to **chronic infections** (e.g., hepatitis B and C, HIV). These viruses may establish long-term infections by hiding within host cells or mutating to escape immune detection. Chronic infections can lead to long-term health issues or complications. **5. Latency and Reactivation (for Some Viruses)** - **Latency**: Certain viruses (e.g., herpesviruses) can enter a **latent phase** after the initial infection, where the viral genome remains dormant in specific cells (like neurons) without active replication or symptoms. - **Reactivation**: Under stress or immune suppression, latent viruses can reactivate, leading to recurrent symptoms or viral shedding. This is seen in infections like herpes simplex virus (cold sores) and varicella-zoster virus (shingles). **6. Immunity and Memory** - **Adaptive Immunity**: Following resolution, **memory T and B cells** remain in the body, ready to respond quickly if the virus reappears. This memory response can provide long-lasting immunity and is the basis of vaccination. - **Variable Immunity**: Immunity duration varies---some viruses (like measles) confer lifelong immunity, while others (like influenza) require repeated exposure or vaccination due to frequent mutations. - Introduce key elements of the biological responses to viral infections **1. Innate Immune Response (First Line of Defense)** - **Recognition of Pathogens**: - **Pattern Recognition Receptors (PRRs)**: Cells like macrophages, dendritic cells, and natural killer (NK) cells use PRRs (such as Toll-like receptors) to recognize viral components (e.g., viral RNA or DNA). This recognition triggers early immune responses. - **Interferons (IFNs)**: - Infected cells release **type I interferons (IFN-α and IFN-β)**, which signal neighboring cells to produce antiviral proteins that inhibit viral replication. Interferons also enhance the activity of NK cells and activate other immune cells. - **Natural Killer (NK) Cells**: - NK cells identify and destroy infected cells by recognizing changes in cell surface markers. They release cytotoxic molecules to kill infected cells, helping to control viral spread early on. - **Inflammation**: - Cytokines released by immune cells increase **inflammation**, which attracts additional immune cells to the site of infection. This inflammatory response helps contain the virus but can also contribute to symptoms like fever and tissue damage. **2. Adaptive Immune Response (Specific and Long-Lasting)** - **Activation of T Cells**: - **Helper T Cells (CD4+ T Cells)**: These cells recognize viral antigens presented by antigen-presenting cells (APCs) and secrete cytokines that help coordinate the immune response. - **Cytotoxic T Cells (CD8+ T Cells)**: Once activated, they seek out and kill virus-infected cells by recognizing viral peptides presented on the cell surface, which helps clear the infection. - **B Cells and Antibody Production**: - **B Cells** recognize viral antigens and, with helper T cell assistance, differentiate into **plasma cells** that produce specific antibodies. Antibodies can neutralize viruses by binding to them and preventing them from entering host cells. They also label viruses for destruction by other immune cells. - **Memory Cells**: - After the infection is cleared, some T and B cells remain as **memory cells**. These cells provide long-term immunity, allowing the body to respond faster and more effectively if the virus is encountered again. **3. Viral Evasion Mechanisms** Viruses often evolve mechanisms to evade or suppress the immune system, such as by **mutating** to escape recognition, **blocking interferon signaling**, or **hiding** within host cells. This can lead to chronic infections or recurrent infections in the case of some viruses. - Recognise oral features of the 'common viral infections of childhood', cold, flu, COVID-19, measles, mumps, rubella, chicken pox, other herpetic infections etc. HPV: - Human papillomavirus - Benign neoplasia - \>70 types (many not all cause warts) - dsDNA - non-enveloped virus - not lytic necessarily but can become lytic with virions to become transmissible - cancer related to virus causes DNA dmg -\> increased expression of oncoproteins E6 + E7 -\> inhibit apoptosis - spread by contact/auto-inoculation - long incubation period -\> up to 12 months for wart to appear - 50% disappear in 6months, 90% in 2 years - Foot (verruca) and finger warts common in children - Oral = squamous papilloma -\> shouldn't be present in children Common cold: - \>100 viruses - Rhinovirus most common - ssRNA - non-enveloped - spread by direct contact/droplets - lytic replication - children main carriers - paramyxoviridae -\> 3 types; paramyxovirus, pneumovirus, morbillivirus - adenovirus; common virus causing flu-like symptoms - orthomyxovirus = influenza A, B, C influenza: - orthomyxovirus - ssRNA - enveloped virus - lysogenic cycle - parainfluenza virus - respiratory syncytial virus (RSV) - enterovirus - types A and B have emergence of new strains SARS-CoV-2: - ssRNA - enveloped virus - symptoms less severe in children - spread by contact/droplets - lysogenic cycle - ulcers, 'COVID-tongue', ulcers, erosions, bullae, vesicles, mucosal pustules, macules, papules and pigmentations, haemorrhgic manifestations, crusts, spontaneous bleeding hand foot and mouth -- picornavirus, ssRNA non-enveloped virus rubella -- rubivirus, enveloped ssRNA virus measles -- paramyxovirus, enveloped ssRNA virus mumps -- paramyxovirus, enveloped -ssRNA virus chicken pox -- varicella, enveloped dsDNA virus GENES 3 Monogenic disorders: - mutation of 1 gene = mendelian inheritance - autosomal dominant - autosomal recessive - X-linked Cystic fibrosis: - Monogenic inheritance - 1:2500 - 1:25 ppl carry the gene - Autosomal recessive - Lifelong disease -\> significant reduction in life expectancy - Symptoms: respiratory + digestive problems -\> thick sticky mucus - ΔF508 mutation in CFTR gene -\> chloride ion transporter - Deletion of 3 DNA bases = missing F (phenylalanine) at position 508 - One missing F = misfold = degraded in the ER - Doesn't reach plasma membrane of cell = CF - Treat symptoms not disease - Mucus broken down using Pulmozyme, breathing improved by physiotherapy, antibiotics for chest infections, sometimes bronchodilators, annual flu jabs - Lumacaftor + Ivacaftor targets mutation -\> interact w channel protein - Lumacaftor corrects misprocessing of CFTR = more protein on cell surface - Ivacaftor increases chance of channels being open (functional) = more chloride flow, hydrated mucus = easier to flow Sickle cell disease - Autosomal recessive - Pain attacks, anaemia, organ dmg - Shortened life expectancy (40-60) - Common in malaria areas - Change of 1 base in beta globin gene -\> replaces glutamate (hydrophilic) with valine (hydrophobic) - Managed with painkillers, antibiotics and blood transfusions - Stem cell + bone marrow treatments risky Duchenne muscular dystrophy - Progressive muscle weakness as muscles break down - Life expectancy \~ late 20's -\> respiratory muscles involved - \~2500 ppl in UK - Recessive X-linked -\> mostly men - Dystrophin = protein that keeps muscle cells intact - Break down with use -\> including respiratory muscles - No cure Polygenic/multifactorial disease - Multiple genes + environmental factors - Don't show simple inheritance factors - Hypertension, schizophrenia, diabetes, asthma Pharmacogenomics - Gene differences determine how body process drugs -  **Genetic Variations Affect Drug Metabolism**: - Some people process drugs faster or slower due to variations in genes encoding enzymes (e.g., *CYP450 enzymes* in the liver). - **Example**: A variation in the *CYP2C19* gene can affect how someone metabolizes the blood thinner **clopidogrel**, impacting its effectiveness. -  **Genetics Can Influence Drug Targets**: - Drugs work by interacting with specific proteins or receptors in the body, which can vary between individuals. - **Example**: In cystic fibrosis, drugs like **ivacaftor** are effective only for patients with specific mutations (e.g., G551D) in the **CFTR gene**. -  **Genetics Can Predict Side Effects**: - Certain genetic markers can indicate a higher risk of adverse drug reactions. - **Example**: Variations in the *HLA-B* gene can predict severe reactions to drugs like **abacavir** (for HIV) or **carbamazepine** (for epilepsy). -